High mobility group 1 protein (HMGB1) is a chromatin component that is either passively released from necrotic cells or actively secreted in response to angiogenic and inflammatory signals. HMGB1 itself may signal through the receptor for advanced glycation end products (RAGE), and via the Toll-like receptors, TLR2 and TLR4. HMGB1 functions as a late mediator of immune response. Apoptotic cells also release HMGB1 but in an oxidized form that does not trigger the immune response.